Kathi Malone and colleagues associate oral contraceptive use with high risk of triple-negative breast cancer in young women

While oral contraceptives are an effective means of preventing pregnancy, they may also raise the risk of a relatively rare but aggressive and difficult-to-treat form of breast cancer in women age 40 and younger.

A new Hutchinson Center study reveals that a year or more of oral contraceptive use was associated with a 4.2-fold increased risk of triple-negative breast cancer for women 40 and under. Longer duration of use and early age of first use further increased risk. Researchers did not find increased risk from pill use among women 41 to 45 years of age.

The population-based study of nearly 900 breast cancer cases, the largest of its kind to evaluate breast cancer subtypes and etiologic differences in young women, was published April 1 in the journal Cancer Epidemiology Biomarkers & Prevention.

"Two things took us by surprise in this study once we sorted the cases into triple negative or not triple negative,” said Dr. Kathi Malone, a Public Health Sciences Division epidemiologist and senior author of the study. “First, it appears that most of the increased risk in this age group related to pill use was confined to the relatively small fraction of cases with triple-negative breast cancer and second, the risk associated with pill use for triple-negative cases was quite large—four- to five-fold increases in risk. Outside of radiation and the BRCA1/BRCA2 genes, these are considerably higher risks than we tend to see in breast-cancer studies."

Triple-negative breast cancer refers to a specific subtype of breast cancer that lacks three key receptors known to fuel most types of breast cancer: estrogen receptor, progesterone receptor, and human epidermal growth factor. Though rare, triple-negative breast cancer is particularly aggressive and generally has a poorer prognosis than other types of breast cancer. In addition, since some of the most successful treatments for breast cancer target these receptors, this type of cancer has fewer treatment options. It is diagnosed more frequently in women who are younger, African American, and BRCA1 carriers. Triple-negative cases account for 10 percent to 17 percent of all breast cancers.

In the study, Malone and colleagues looked at a broad range of known and suspected breast cancer risk factors among women 45 years of age and younger, including family history of breast cancer, body mass index, and tobacco and alcohol use; reproductive history, including age at menarche and lactation history; and oral contraceptive use.

”While we do not yet know the mechanism through which oral contraceptive use may affect breast-cancer risk in young women, this research could stimulate new ideas regarding the etiologic pathway for triple-negative disease,” said Jessica Dolle, the study’s first author.

The strong association between birth control use and risk of triple-negative breast cancer observed in this study, coupled with the scarcity of other such studies to date, emphasizes the need for future research and the preliminary nature of these results, Malone said.

The National Institutes of Health funded the study. Co-authors include David Doody and Drs. Janet Daling and Emily White, all of PHS; Dr. Peggy Porter, Human Biology and PHS divisions; and the National Cancer Institute’s Dr. Louise Brinton.